This proposal requests funding for a Q-Exactive Orbitrap LC-MS/MS system to be placed in the Mass Spectrometry Facility of the Department of Chemistry and Biochemistry at the University of Delaware. To maximize the utility of this workhorse instrument, it will be configured with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources, as well as a conventional-flow LC with fast column- switching capabilities and a nano-LC for analysis of peptides. This instrument will provide research capabilities that are currently lacking at the University of Delaware (UD). Currently, researchers at UD have no on-site or in-state access to high-resolution accurate mass mass spectrometry (HRMS) instruments for characterization of small molecules. This instrument will provide this crucial tool to these researchers. Further, the Orbitrap LC- MS/MS will enable MS analysis of protein and peptide samples essential for many biomedical research programs at UD. The high sensitivity and broad coverage of the Orbitrap LC-MS/MS will be superior to that of the aging Q-ToF instrument, which is in continuous use by UD researchers. A well-defined management plan and high level of institutional commitment ensure the sustainability of this broadly used instrument. The proposed instrument will provide critical support for NIH-funded research programs of 6 major and 7 minor users spanning biochemistry, chemistry and materials science. The LC-MS/MS will greatly enable advances across a wide range of biomedical research areas, including structural enzymology, synthetic method development, protein assemblies, signaling and regulatory pathways for enzymes, molecular design, materials science for tissue regeneration and diagnostic devices, and chemical probe discovery. The instrument will also provide support to several major NIH initiatives at the University of Delaware, including the Chemistry-Biology Interface (CBI) Training Program, multiple Centers of Biomedical Research Excellence (COBRE) on Delaware's campus, the Delaware IDeA Network of Biomedical Research Excellence (INBRE), and the Center for Translational Cancer Research (CTCR).